Is there a relationship between KRAS and panitimumab?

This study examined whether combination treatment panitumumab (Vectibix) and FOLFOX4 can improve the outcome of patients.

Patients with mutated KRAS colorectal cancer have a genetic mutation in KRAS, an important gene in various signaling pathways. Patients with normal (non-mutated or wild-type) KRAS have no mutation in the gene. Treatment for colorectal cancer can often be more or less efficient dependent on which version of this gene is present.

Previous studies have shown that the biologic drug panitumumab (Vectibix), combined with the chemotherapy treatment FOLFOX4 (5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin (Eloxatin)), improves the outcome of patients with previously untreated, normal KRAS metastatic colorectal cancer. Metastatic colorectal cancer occurs when the cancer has spread beyond the colon or the rectum. However the long-term benefits of panitumumab have not yet been reported.

This study included 1,183 patients; 60% had normal KRAS and 40% had a KRAS mutation. Patients were assigned to one of two treatments: panitumumab 6.0 mg/kg every 2 weeks plus FOLFOX4 or FOLFOX4 alone. Effectiveness and safety were monitored for 30 months after the last patient was enrolled.

The outcome of patients with normal KRAS improved with pantitumumab treatment; this was not seen in those with mutated KRAS.

For those with normal KRAS, the average time following treatment before the disease progressed was 10.0 months for panitumumab and FOLFOX4 compared to 8.6 months for FOLFOX4 alone. The average overall survival for normal KRAS was 23.9 months for panitumumab and FOLFOX4 compared to 19.7 months for FOLFOX4 alone.

Approximately 19% of patients discontinued panitumumab due to their experience of adverse events (any unfavorable and unintended sign, symptom, or disease potentially associated with the use of a medical treatment or procedure). The most notable severe adverse events were skin reactions, in 31 – 37% of patients.

The authors concluded that the addition of panitumumab to FOLFOX4 therapy, as a first-line treatment of normal KRAS metastatic colorectal cancer, improves patient outcome.

The study was funded by Amgen Inc, who also manufacture panitumumab.

When considering treatment for metastatic colorectal cancer, discuss your KRAS mutation status and the use of panitumumab with your doctor.